Continued studies of the role of the retinal pigment epithelium (RPE) in the pathogenesis of proliferative vitreoretinopathy (PVR) are proposed. Our recent studies suggest the importance of hepatocyte growth factor (HGF) and connective tissue growth factor (CTGF) in PVR. A new model of PVR pathogenesis will be tested which incorporates the following HYPOTHESES: (1) The formation of invasive multilayered groups of RPE from an intact monolayer is mediated in part by HGF expressed by RPE. (2) Transformation of cellular RPE membranes into densely fibrotic membranes is mediated in part by CTGF. Specific Aims to test these hypotheses are: The cellular and molecular mechanisms by which (1) HGF stimulates the formation of multilayered groups of RPE from the monolayer, and (2) CTGF induces transformation of epiretinal membranes from cellular to fibrotic will be determined. (3) The effects of over-expression or inhibition of HGF and/or CTGF on the development of PVR invivo will be determined. Accomplishment of these aims may open new strategies of therapy for PVR, a blinding complication of eye injury or retinal detachment surgery.